سکرتوم مشتق از سلول های بنیادی مزانشیم مهندسی شده باNrf2 باعث مقاومت MSC در برابر استرس اکسیداتیو می شود

Title

Secretom derived from Nrf2- engineered mesenchymal stem cells protects MSCs against oxidative stress

English Abstract

Introduction: Recent studies have proposed cell therapy as a promising therapeutic strategy for treating many types of disease. Among different cell types, MSCs have been explored as therapeutic tools for a large variety of indications. Although the benefits of MSCs in regeneration and repair of tissues are clearly demonstrated, massive cell death during few days after transplantation limit their overall effectiveness and significantly affect their clinical usage. Hence, development of strategies to improve cell survival in vivo is a major challenge. For overcoming this limitation, genetically modification of MSC by anti-apoptotic and cytoprotective genes has recently been shown to be highly efficient method but there are still concerns to use them in clinical trials. Objectives: Therefore, we hypothesized that culture of MSCs in the presence of secretome of genetically manipulated cells by one of the cytoprotective gene i.e. Nrf-2 maybe improve cell survival. Materials & Methods: In this study, we manipulate bone marrow derived mesenchymal stem cells nuclear factor erythroid2-related factor 2 (Nrf2) gene. NrF2 is a transcription factor regulates the expression of many antioxidants. Then we cultivate another group of MSCs in the condition medium derived from Nrf2 manipulated cells called secretome. Next, the viability and apoptosis of these cells have evaluated following oxidative stress exposure. Results: Secretome derived from Nrf2 manipulated cells protect MSCs against cell death and the apoptosis induced by oxidative stress conditions. Conclusions: Our results suggested that cultivation of MSCs in Nrf2-MSC secretome can be improve cell survival and maybe an appropriate strategy to overcome the limitation of genetically manipulated MSCs. This finding could be use as a novel strategy for enhancing cell engraft and open new window for clinical application of MSCs.

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